Introduction

Chemotherapy remains a standard treatment option for metastatic triple-negative breast cancer (TNBC) but is associated with limited survival. Although some targeted antibody–drug conjugates have demonstrated clinical benefits and are considered standard therapy, persistent unmet medical needs remain due to varying accessibility. The OptiTROP-Breast01 phase 3 trial assessed sacituzumab tirumotecan (sac-TMT) versus chemotherapy in patients with locally recurrent or metastatic TNBC who had received two or more prior therapies, including at least one for metastatic disease. Patients were randomized to sac-TMT (n = 130) or chemotherapy (n = 133). The primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) was met based on the protocol-specified interim analysis. At final analysis, the median PFS by BICR was 6.7 (95% confidence interval (CI), 5.5–8.0) months with sac-TMT and 2.5 (95% CI, 1.7–2.7) months with chemotherapy (hazard ratio (HR), 0.32; 95% CI, 0.24–0.44; P < 0.00001). Concurrently, at the protocol-specified interim analysis for overall survival (OS), the median OS was not reached (95% CI, 11.2 months to not estimable (NE)) with sac-TMT and 9.4 (95% CI, 8.5–11.7) months with chemotherapy (HR, 0.53; 95% CI, 0.36–0.78; P = 0.0005). The percentage of patients with an objective response was 45.4% with sac-TMT and 12.0% with chemotherapy. The median duration of response was 7.1 (95% CI, 5.6–NE) months with sac-TMT and 3.0 (95% CI, 2.5–NE) months with chemotherapy. The most common treatment-related adverse event with sac-TMT was hematologic toxicity. Sac-TMT demonstrated statistically significant and clinically meaningful improvements in PFS compared to chemotherapy, with a manageable safety profile. The study findings support sac-TMT as an additional effective treatment option for pretreated metastatic TNBC. ClinicalTrials.gov identifier: NCT05347134.